The ultimate goal of our research is to determine the properties and localization of the kappa opioid receptor. The existence of this receptor has primarily been established by peripheral tissue bioassay and behavioral techniques. Attempts to identify the receptor by radioreceptor techniques have been complicated by an anomalous lack of receptor selectivity displayed by kappa agonists in brain membranes. As a result considerable controversy surrounds the proposed existence of kappa receptors within the CNS. In this proposal we shall outline experiments designed to resolve this controversy. The anomalous discrepancy between peripheral tissue bioassay and radioreceptor assay data will be examined in detail. We shall also outline alternative approaches for determining the molecular nature and distribution of kappa receptors in central and peripheral tissues. The significance ofthis work lies in its contribution to our fundamental knowledge of opioid receptor pharmacology. There may also be important clinical implications as regards the development of selective therapeutic agents.